Title:
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Psychopathology and cognition as markers of risk for bipolar disorder
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Bipolar disorder (BD) is a fairly common, highly heritable psychiatric disorder which can be highly disabling to those who suffer from it. There is a limited understanding of early precursors to BD that might be helpful to inform prediction models and knowledge of aetiology. Few population-based longitudinal studies have examined associations between measures of childhood psychopathology/cognitive functioning and BD, or phenotypic manifestations of increased genetic risk for BD in childhood. I investigated whether childhood psychopathology and cognitive domains examined from ages 8-11 years were associated with hypomania examined at ages 22-23 years. I then conducted a systematic review to identify phenotypes associated with genetic risk for BD, measured using a polygenic risk score (PRS) approach. Finally, I investigated whether increased genetic risk for BD, using a BD-PRS, was associated with various psychopathology and cognitive domains in childhood and hypomania in young adulthood. Findings from Chapter 4 suggest that borderline personality disorder (BPD) traits in childhood are strongly associated with hypomania, particularly the ‘risk-taking/irritable’ factor. Better performance in the domains of working memory, problem solving ability, verbal learning and emotion recognition are also associated with hypomania, with stronger association with the ‘active/elated’ factor (Chapter 5). Findings from Chapter 6 highlight a limited literature on phenotypic manifestations of increased genetic risk for BD in childhood/adolescence. Individuals with increased genetic risk for BD are more likely to have ADHD, and have poorer executive functioning, processing speed and performance IQ in childhood (Chapters 7 and 8). This thesis adds to a limited literature examining associations between measures of childhood psychopathology/cognition and hypomania in the general population, and about how increased genetic risk for BD is manifest in childhood/adolescence. Further work to examine the robustness of these findings in other populations at various stages of development are required, and to elucidate the mechanisms that underlie the associations observed.
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